La. Hogarth et Ag. Hall, Increased BAX expression is associated with an increased risk of relapse in childhood acute lymphocytic leukemia, BLOOD, 93(8), 1999, pp. 2671-2678
Studies in cell lines have indicated that expression of the BCL-2 family of
proteins is an important determinant of chemotherapy-induced apoptosis; ho
wever, the level of expression of these proteins in childhood acute lymphob
lastic leukemia (ALL) has not been extensively reported. Using quantitative
Western blotting we have determined the level of expression of BCL-9, BAX,
MCL-1, and BCL-X in lymphoblasts from 47 children with ALL (33 at presenta
tion only, 4 at relapse only, and 10 at both presentation and on relapse).
Results were determined as a ratio to actin as an internal control. BCL-2.
BAX, and MCL-1 were detected in all samples. BCL-X-L was only detected in 6
cases (4 at presentation and 2 at relapse) and BCL-X-S in none. No correla
tion was found between expression and white blood cell count, age at diagno
sis, gender, or blast karyotype. BCL-2 levels and the BCL/BAX and MCL-1/BAX
ratios were found to be significantly higher in B-lineage as compared with
T-lineage disease (P < .003, .02, and .02, respectively). No consistent pa
ttern of change in expression was noted in the 10 cases studied at both pre
sentation and relapse. Kaplan-Meier analysis showed a significant correlati
on between high BAX expression and an increased probability of relapse (P <
.05 by the log rank test), suggesting that chemosensitivity in leukemic bl
asts may be regulated by factors that override the BCL-2 pathway. (C) 1999
by The American Society of Hematology.